1. Field of the Invention
The present invention relates to novel chiral biaryl phosphines and chelating phosphines with tunable bite angles for applications in asymmetric catalysis. More particularly, the present invention relates to transition metal complexes of these ligands, which are useful as catalysts in asymmetric reactions.
2. Description of the Prior Art
Discovery of new chiral ligands is crucial in developing highly enantioselective transition metal-catalyzed reactions. Despite the large number of chiral ligands that have been made for applications in asymmetric catalysis, only few chiral ligands or synthetic routes or motifs have been commonly used in the synthesis of chiral molecules by the chemical industry or academic laboratories.
Among these ligands, BINAP is one of frequently used chiral ligands. The axially dissymmetric, fully aromatic BINAP have demonstrated to be highly effective for many asymmetric reactions (Noyori, R; Takaya, H. Acc. Chem. Res. 1990, 23, 345; Olkuma, T.; Koizumi, M.; Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa, T.; Ikariya, T.; Noyori, R J. Am. Chem. Soc. 1998, 120, 13529). Related axially dissymmetric ligands such as MeO-BIPHEP and BIPHEMP were made and used for a number of asymmetric reactions (Schmid, R. et al. Pure and Appl. Chem. 1996, 68, 131; Foricher, J.: Heiser, B.; Schmid, R. U.S. Pat. No. 5,302,738; Michel, L.; European Patent Application 0667350A1; Broger, E. A.; Foricher, J.; Heiser, B.; Schmid, R. PCT WO 92/16536). Several chiral biaryl phosphines known in the literature are depicted below. 
Despite the extensive research in this area, there are still a variety of reactions in which only modest enantioselectivity has been achieved with these ligands. Specially, the free rotation in certain degrees makes BINAP as a conformationally flexible ligand. Recent results suggest that partially hydrogenated BINAP with a bigger bite angle, i.e., H8-BINAP, may be a better ligand in certain asymmetric reactions.
For example, restricting conformational flexibility can enhance enantioselectivity (Uemura, T.; Zhang, X.; Matsumura, K.; Sayo, N.; Kumobayashi, H.; Ohta, T.; Nozaii, K.; Takaya, H. J. Org Chem. 1996, 61, 5510). For most chiral axially dissymmetric phosphine ligands, there is a low energy bite angle dictated by the metal species and a large degree of free rotation. The bite angle of chelating chiral phosphines is difficult to fine-tune. Change of ligand electronic properties can also contribute to the activity as well as to the enantioselectivity of a reaction. Because different substrates require different size of chiral pockets, it is important to have a tunable chiral ligand system to achieve high enantioselectivity.
The present invention includes tunable chiral biaryl phosphine ligands with a variety of bite angles by lining two aryl groups with a variety of bridges. Several new chiral biaryl phosphines are disclosed. To achieve heterogenous and supported catalysts, a number of approaches to ligand systems have been developed. These include linking these ligands to a polymer chain, organic or inorganic supports such as dendrimers, silica gel and molecular sieves. Water-soluble groups can be easily introduced into the ligands and fluorocarbon chains can be introduced to promote phase separation.
Catalysts derived from the ligands of the present invention are employed in a variety of asymmetric reactions such as hydrogenation, hydride transfer reaction, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, isomerization, allylic alkylation, cyclopropanation, Diels-Alder reaction, Aldol reaction, Heck reaction and Michael addition to prepare asymmetric compounds having high enantiomeric purity.
The present invention includes a ligand selected from the group consisting of compounds represented by A through Z, AA, BB and CC: 
wherein xe2x80x9cbridge 1xe2x80x9d is selected from the group consisting of: Cxe2x95x90O, Cxe2x95x90S, SO2, PO(OR1), PO(NHR1), PO(NR1R2), divalent phenyl, substituted divalent phenyl, 2,2xe2x80x2-divalent-1,1xe2x80x2-biphenyl, substituted 2,2xe2x80x2-divalent-1,1xe2x80x2-biphenyl, 2,2xe2x80x2-divalent-1,1xe2x80x2-binaphthyl, substituted 2,2xe2x80x2-divatent-1,1xe2x80x2-binaphthyl, 1,1xe2x80x2-ferrocene, substituted 1,1xe2x80x2-ferrocene, SiR12 (CH2)n where n is an integer ranging from 1 to 8, and (CR22)nX1(CR22)m wherein each n, m is independently an integer from 1 to 8, wherein X1 is selected from the group consisting of O, S, NR3, PR32, +NR32, +PR32, divalent aryl, divalent fused aryl, divalent 5-membered ring heterocyclic group and divalent fused heterocyclic group;
wherein xe2x80x9cbridge 2xe2x80x9d is selected from the group consisting of: NH, O, a single bond, (CH2)n, O(CH2)nO, NH(CH2)nNKn wherein each n is independently an integer from 1 to 8, divalent phenyl, substituted divalent phenyl, divalent phenyl amine, substituted divalent phenyl amine, 2,2xe2x80x2-divalent-1,1xe2x80x2-biphenyl, substituted 2,2xe2x80x2-divalent-1,1xe2x80x2-biphenyl, 2,2xe2x80x2-divalent-1,1xe2x80x2-binaphthyl, substituted 2,2xe2x80x2-divalent-1,1xe2x80x2-binaphthyl, 1,1xe2x80x2-ferrocene, substituted 1,1xe2x80x2-ferrocene, O(CR22)nX1(CR22)mO, NH(CR22)nX1(CR22)mNH and (CR22)nX1(CR22)m wherein each n, m is independently an integer from 1 to 8, wherein X1 is selected from the group consisting of: O, S, NR3, PR32, +NR32, +PR32, divalent aryl, divalent fused aryl, divalent 5-membered ring heterocyclic group and divalent fused heterocyclic group;
wherein xe2x80x9cbridge 3xe2x80x9d is selected from the group consisting of: SO2, CO, COCO, OC(CH2)nCO, (CH2)n wherein n is an integer ranging from 1 to 8, COArCO, wherein Ar is selected from the group consisting of: divalent phenyl, substituted divalent phenyl, 2,2xe2x80x2-divalent-1,1xe2x80x2-biphenyl, substituted 2,2xe2x80x2-divalent-1,1xe2x80x2-biphenyl, 2,2xe2x80x2-divalent-1,1xe2x80x2-binaphthyl, substituted 2,2xe2x80x2-divalent-1,1xe2x80x2-binaphthyl, 1,1xe2x80x2-ferrocene, substituted 1,1xe2x80x2-ferrocene and CO(CR22)nX1(CR22)mCO wherein each n, m is independently an integer from 1 to 8, wherein X1 is selected from the group consisting of: O, S, NR3, PR32, +NR32, +PR32, divalent aryl, divalent fused aryl, divalent 5-membered ring heterocyclic group and divalent fused heterocyclic group;
wherein each R1 is independently selected from the group consisting of: aryl, alkyl, alkaryl, araly and substituted derivatives thereof wherein the substituent in said substituted derivatives is selected from the group consisting of: carboxylic acid, alkoxy, hydroxy, alkylthio, thiol and dialkylamino;
wherein each R2 and R3 is independently selected from the group consisting of: aryl, alkyl, substituted aryl and substituted alkyl group;
wherein each said substituted divalent phenyl, divalent phenyl amine, biphenyl, binaphthyl and ferrocene derivative comprises at least one substituent selected from the group consisting of aryl, substituted aryl, alkyl, heteroatom, F, Cl, Br, I, COOR1, SO3R1, PO3R12, OR1, SR1, PR12, AsR12, SbR12, OAr, nitro, amino, vinyl, substituted vinyl and sulfonic acid;
wherein each R and Rxe2x80x2 is independently selected from the group consisting of: aryl, alkyl, alkaryl, arallkyl and substituted derivatives thereof, wherein the substituent in said substituted derivatives is selected from the group consisting of: carboxylic acid, alkoxy, hydroxy, alkylthio, thiol, dialkyl amino groups;
wherein each X and Xxe2x80x2 is independently selected from the group consisting of aryl, alkyl, alkaryl, aralkyl, alkoxy, alkoxy, hydroxy, alkylthio, thiol, primary amine, secondary amine and ArNH;
wherein each Z and Zxe2x80x2 is independently selected from the group consisting of: halogen, alkyl, aryl, aryloxy, nitro, amino, vinyl, substituted vinyl and sulfonic acid; and
wherein each Q, Qxe2x80x2, Y, Yxe2x80x2, T and Txe2x80x2 is independently selected from the group consisting of aryl, alkyl, alkaryl, aralkyl and substituted derivatives thereof, wherein the sub stituent in said substituted derivatives is selected from the group consisting of: carboxylic acid, alkoxy, hydroxy, alkylthio, thiol and dialkylamino.
The present invention further includes a catalyst prepared by a process comprising contacting a transition metal salt, or a complex thereof, and a ligand selected from the group consisting of compounds represented by A through Z, AA, BB and CC, as described above.
The present invention still further includes a process for preparation of an asymmetric compound using a catalyst according to the present invention. The process comprises contacting a substrate capable of forming an asymmetric product by an asymmetric reaction and a catalyst prepared by a process comprising contacting a transition metal salt, or a complex thereof, and a ligand selected from compounds represented by A through Z, AA, BB and CC, as described above. The transition metal complexes of the chiral ligands of the present invention produce chiral products with an extremely high enantioselectivity. For example, ruthenium complex of chiral C4-TunaPhos ligand reduces isopropyl acetoacetate with 99% enantioselectivity to produce the corresponding alcohol in a 99% ee.